Natural production of numerous agents, metabolites, enzymes, and other secretions occur within a living being host as physiological events take place. One such event is the metabolism of carbohydrates to glucose, which is mainly controlled by insulin produced by the beta cells of the islets of Langerhans within the pancreas. Insulin is necessary in maintaining glucose homeostasis. In addition to its principal role in carbohydrate metabolism, insulin also significantly affects lipid, protein, and mineral metabolism. When efficient insulin production by the pancreas is inhibited or terminated and therefore is insufficient, as occurs substantially in Type I diabetes, for example, where immune system of the host destroys beta cells of the islets of Langerhans, insulin from another source must be provided or the affected individual will suffer from many severe consequences of diabetes mellitus. The dispensation of medicament is determined by live secretory cells in response to physiological make-up of host tissue fluid in contact with the secretory cells. Thus, in the case of a diabetes patient, insulin would be dispensed whereas chemotherapeutic drugs would be dispensed in the case of cancer. In these and other similar circumstances, it is highly beneficial to the patient when automatic dispensing of the medicament occurs, without the need to resort to pills, injections or other discomforting means of medication. A special unit can be implanted within the patient. This unit consists of a reservoir of living cells, of type determined by patient's needs, and the live cells act in response to the body fluids perfusing through them. The implanted unit will have a supply of live cells that will be active for 4 years, a micropump and associated electronics to circulate the perfusion fluid, a wireless transmitter to communicate with the unit and an inductively rechargeable battery.
Prior-art approaches for providing insulin to maintain proper plasma glucose concentrations are numerous. One of the most commonly employed approaches is the injection of insulin into the patient a plurality of times daily in response to plasma-glucose monitoring. Subcutaneous injection is a usual insulin introduction route, but is flawed and/or disfavored for several reasons. In particular, injection administration is limited because there is no direct feedback between blood glucose level and the dosage of insulin. In addition, there is poor patient acceptance, significant absorption variability among patients, potential overdosing resulting in hyperinsulinemia/hypoglycemia, potential underdosing resulting in hypoinsulinemia/hyperglycemia, formation of anti-insulin antibodies, hypersensitivity reactions due to insulin formulations, and other untoward occurrences. Relatively new jet injector devices, as opposed to traditional syringes, do not appreciably avoid syringe-injection limitations as noted above. Orally administered insulin finds poor effectiveness because of the vast variability found in digestive processes and digestion states among patients.
Another prior art approach for providing insulin to patients is the use of wearable or implantable insulin pumps, which are pre-programmed and pre-loaded with insulin and do not allow direct feedback of the optimal dosage. These pumps can also cause both mechanical and physiological problems for the patient. With respect to the former problem, these pumps can experience catheter blockage, infection, skin inflammation, erosion, local fluid accumulation, dislocation due to patient physical activity, and required regular refills of insulin usually at monthly or bimonthly intervals. With respect to the latter problem, presently available insulin pumps do not have reliable glucose sensors and therefore, are unable to precisely dispense a needed insulin quantity for proper plasma-glucose level maintenance. In addition, presently available insulin pumps do not have reliable glucose sensors and therefore, are unable to precisely dispense a needed insulin quantity for proper plasma-glucose level maintenance.
New methods for treating insulin-dependent diabetes mellitus are presently being sought. Although it is possible to transplant a pancreas from one human to another, the survival rate for this procedure is only 40% at one year following surgery. Researchers have also used isolated pancreatic islets in transplantation approaches in attempts to find a viable long term treatment of diabetes.
The islets of Langerhans are clusters of differentiated cells sharing a common precursor. Found in the pancreas of mammals, islet cells taken together can be considered as a single endocrine organ. The islet cells occupy about 7% of the human pancreas, which also contains the exocrine acinar tissue. The composition of cells in the islets differ depending on the location of the islet in the pancreas. Central to each islet is a core of insulin secreting beta cells. Surrounding the beta cells are somatostatin secreting delta cells, glucagon secreting alpha cells and pancreatic polypeptides containing F-cells. Alpha cells tend to be concentrated in the tail and the body of the pancreas whereas the F-cells are concentrated in the head. This distribution corresponds to the embryonic origin of alpha and F-cells from dorsal and ventral primordium of the pancreas. Transplantation of pancreatic beta cells has been done to the pancreas, liver, muscles, or peritoneal cavity of the patient, or the transplantation of an entire donor-pancreas as a replacement. Such an approach, however, is not practical because of recipient immune-rejection, limited availability of donor organs, and other restraints on patient acceptance.
In view of the above inability of prior art approaches to artificially provide a natural imitation of a physiological secretion, it is apparent that highly important and unfulfilled needs exist first for sensing an in vivo demand for a secretory product; and second for fulfilling that requirement by providing an appropriate quantity of secretory product.